AUTONOMOUS DEVELOPMENTAL CONTROL OF HUMAN EMBRYONIC GLOBIN GENE SWITCHING IN TRANSGENIC MICE

被引:116
作者
RAICH, N [1 ]
ENVER, T [1 ]
NAKAMOTO, B [1 ]
JOSEPHSON, B [1 ]
PAPAYANNOPOULOU, T [1 ]
STAMATOYANNOPOULOS, G [1 ]
机构
[1] UNIV WASHINGTON, DEPT MED GENET, SEATTLE, WA 98195 USA
关键词
D O I
10.1126/science.2251502
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
The mechanisms by which expression of the β-like globin genes are developmentally regulated are under intense investigation. The temporal control of human embryonic (ε) globin expression was analyzed. A 3.7-kilobase (kb) fragment that contained the entire human ε-globin gene was linked to a 2.5-kb cassette of the locus control region (LCR), and the developmental time of expression of this construct was studied in transgenic mice. The human e-globin transgene was expressed in yolk sac-derived primitive erythroid cells, but not in fetal liver or bone marrow-derived definitive erytiroid cells. The absence of ε gene expression in definitive erythroid cells suggests that the developmental regulation of the ε-globin gene depends only on the presence of the LCR and the ε-globin gene itself (that is, an autonomous negative control mechanism). The autonomy of ε-globin gene developmental control disfinguishes it from the competitive mechanism of regulation of γ and β-globin genes, and therefore, suggests that at least two distinct mechanisms function in human hemoglobin switching.
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页码:1147 / 1149
页数:3
相关论文
共 21 条
[1]   THE PRIMARY STRUCTURE OF THE HUMAN EPSILON-GLOBIN GENE [J].
BARALLE, FE ;
SHOULDERS, CC ;
PROUDFOOT, NJ .
CELL, 1980, 21 (03) :621-626
[2]   RAPID REPROGRAMMING OF GLOBIN GENE-EXPRESSION IN TRANSIENT HETEROKARYONS [J].
BARON, MH ;
MANIATIS, T .
CELL, 1986, 46 (04) :591-602
[3]   HUMAN GAMMA-GLOBIN TO BETA-GLOBIN GENE SWITCHING IN TRANSGENIC MICE [J].
BEHRINGER, RR ;
RYAN, TM ;
PALMITER, RD ;
BRINSTER, RL ;
TOWNES, TM .
GENES & DEVELOPMENT, 1990, 4 (03) :380-389
[4]   IDENTIFICATION OF A TRANSCRIPTIONAL SILENCER IN THE 5'-FLANKING REGION OF THE HUMAN EPSILON-GLOBIN GENE [J].
CAO, SX ;
GUTMAN, PD ;
DAVE, HPG ;
SCHECHTER, AN .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1989, 86 (14) :5306-5309
[5]   AN EMBRYONIC PATTERN OF EXPRESSION OF A HUMAN-FETAL GLOBIN GENE IN TRANSGENIC MICE [J].
CHADA, K ;
MAGRAM, J ;
COSTANTINI, F .
NATURE, 1986, 319 (6055) :685-689
[6]   DEVELOPMENTAL REGULATION OF BETA-GLOBIN GENE SWITCHING [J].
CHOI, ORB ;
ENGEL, JD .
CELL, 1988, 55 (01) :17-26
[7]   DEVELOPMENTAL REGULATION OF HUMAN GLOBIN GENES IN TRANSGENIC MICE [J].
COSTANTINI, F ;
RADICE, G ;
MAGRAM, J ;
STAMATOYANNOPOULOS, G ;
PAPAYANNOPOULOU, T ;
CHADA, K .
COLD SPRING HARBOR SYMPOSIA ON QUANTITATIVE BIOLOGY, 1985, 50 :361-370
[8]   DEVELOPMENTAL REGULATION OF HUMAN FETAL-TO-ADULT GLOBIN GENE SWITCHING IN TRANSGENIC MICE [J].
ENVER, T ;
RAICH, N ;
EBENS, AJ ;
PAPAYANNOPOULOU, T ;
COSTANTINI, F ;
STAMATOYANNOPOULOS, G .
NATURE, 1990, 344 (6264) :309-313
[9]   THE HUMAN BETA-GLOBIN LOCUS ACTIVATION REGION ALTERS THE DEVELOPMENTAL FATE OF A HUMAN-FETAL GLOBIN GENE IN TRANSGENIC MICE [J].
ENVER, T ;
EBENS, AJ ;
FORRESTER, WC ;
STAMATOYANNOPOULOS, G .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1989, 86 (18) :7033-7037
[10]   MOLECULAR ANALYSIS OF THE HUMAN BETA-GLOBIN LOCUS ACTIVATION REGION [J].
FORRESTER, WC ;
NOVAK, U ;
GELINAS, R ;
GROUDINE, M .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1989, 86 (14) :5439-5443